rs140764964

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_032968.5(PCDH11X):c.718A>T(p.Thr240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,208,038 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 99 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., 5 hem., cov: 20)

Exomes 𝑓: 0.00025 ( 0 hom. 94 hem. )

Consequence

PCDH11X
NM_032968.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.02

Publications

0 publications found

Variant links:

Genes affected

PCDH11X (HGNC:8656): (protocadherin 11 X-linked) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

PCDH11X links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13381535).

BP6

Variant X-91876958-A-T is Benign according to our data. Variant chrX-91876958-A-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1087134.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5 link	c.718A>T	p.Thr240Ser	missense_variant	Exon 6 of 11	ENST00000682573.1	NP_116750.1	Q9BZA7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1 link	c.718A>T	p.Thr240Ser	missense_variant	Exon 6 of 11		NM_032968.5	ENSP00000507225.1		Q9BZA7-1

Frequencies

GnomAD3 genomes

AF:

0.000300

AC:

AN:

109904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000494

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000352

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000473

Gnomad OTH

AF:

0.000674

GnomAD2 exomes

AF:

0.000229

AC:

AN:

183292

AF XY:

0.000162

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000500

Gnomad NFE exome

AF:

0.000367

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000247

AC:

271

AN:

1098091

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

AN XY:

363565

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26397

American (AMR)

AF:

0.000114

AC:

AN:

35200

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54143

European-Finnish (FIN)

AF:

0.000543

AC:

AN:

40534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.000280

AC:

236

AN:

842010

Other (OTH)

AF:

0.000152

AC:

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000300

AC:

AN:

109947

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

AN XY:

32137

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30253

American (AMR)

AF:

0.000493

AC:

AN:

10133

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3504

South Asian (SAS)

AF:

0.00

AC:

AN:

2528

European-Finnish (FIN)

AF:

0.000352

AC:

AN:

5676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000473

AC:

AN:

52808

Other (OTH)

AF:

0.000665

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000287

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 20, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.718A>T (p.T240S) alteration is located in exon 2 (coding exon 2) of the PCDH11X gene. This alteration results from a A to T substitution at nucleotide position 718, causing the threonine (T) at amino acid position 240 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Jan 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.4

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.032

.;T;.;.;.;.

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.52

T;T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;L;L;L;L

PhyloP100

3.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.69

T;T;T;T;T;T

Sift4G

Benign

0.70

T;T;T;T;T;T

Polyphen

0.0090

B;B;B;B;B;B

Vest4

0.098

MutPred

0.52

Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);Gain of disorder (P = 0.0553);

MVP

0.72

MPC

1.0

ClinPred

0.040

GERP RS

-0.33

Varity_R

0.074

gMVP

0.15

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs140764964

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over